The present invention, in some embodiments thereof, relates to compositions comprising a novel laminin polypeptide and, more particularly, but not exclusively, to matrices and hydrogels comprising same and methods of using same.
Hydrated gels (hydrogels) are viscous, semisolid entities at physiological temperatures and pH which can be used for tissue engineering, regenerative medicine and as biomaterials. For example, hydrogels were prepared from polysaccharides (Coviello et al, 2007) such as hyaluronic acid (e.g., using hybrid combinations of hyaluronic acid with calcium phosphate, chitosan, gelatin or alginate) or chitosan (e.g., chitosan with laminin peptides; Suzuki et. al., 2003; Itoh et. al., 2005; Matzuda et. al., 2005, Ho et. al., 2005) as well as from synthetic materials such as Poly(2-hydroxyethyl methacrylate). Hyaluronic acid-based hydrogels provide a growth supportive milieu for cells and tissues such as for nerve regeneration (Suzuki et. al., 2003; Itoh et. al., 2005), while guiding migration and regeneration of nutritional-trophic and anti oxidative agents.
Laminins are basement membrane glycoproteins which function as adhesive molecules, mediating and interacting with cytoskeleton's bound integrins, cadherins, cell adhesive molecules (CAMs) and extracellular matrix (ECM) constituents and support cell migration, attachment, proliferation, differentiation and survival. Hyaluronic acid-based hydrogels which were modified with laminin were shown to promote neurite extension (Hou et. al., 2005). Certain laminin sequence repeats were found to have a biological activity on cell surface receptors. These include IKVAV (SEQ ID NO:1) and YIGSR (SEQ ID NO:2) which serve as guiding tracks for migration, regeneration and growth (Tashiro et. al., 1989; Powell and Kleinmann, 1997; Niece et. al., 2003; Hallmann et. al., 2005).
The primary defense mechanism against oxidative stress is the enzyme superoxide dismutase (SOD) which catalyzes the dismutation of superoxide anion free radical (O2−) to hydrogen peroxide (H2O2) and oxygen (O2). Hydrogels which include SOD from bovine erythrocytes conjugated to sodium hyaluronate were found to be non-immunogenic in mice and exhibited much higher anti-inflammatory activities than HA or SOD alone (Sekurai et. al., 1997). In addition, SOD was found to inhibit not only reactive oxygen species (ROS) induction but also HA depolymerization which is caused by mechanical stress (Yamazaki et. al., 2003).
Additional background art includes Hartman J R., 1986 (Proc. Natl. Acad. Sci. 83: 7142-7146).